PROJECT SUMMARY/ABSTRACT Herpes zoster (HZ) of the ophthalmic distribution, herpes zoster ophthalmicus (HZO), is the second most common location of HZ and can cause significant morbidity. Patients with HZO may experience permanent vision loss, chronic inflammation requiring long-term therapy, and complications such as cataract, glaucoma, and postherpetic neuralgia. In 2006, the FDA approved a HZ vaccine ( Zostavax ) for immunocompetent adults over age 60, after it was shown to reduce the incidence of HZ by 51%. However, there is a paucity of data regarding its effectiveness against HZO. We aim to determine if the HZ vaccine is as effective in preventing HZO as HZ, and if vaccination affects the severity and disease course of HZO. We propose to use four big data sources to address our questions about HZO and the impact of the HZ vaccine in a ?real-world? setting. To determine the effectiveness of the HZ vaccine at each year post- vaccination, we will use proportional hazards regression with inverse propensity score weighting in the OptumLabs health insurance database, the Veterans Health Administration (VHA) system, and the Kaiser Permanente Hawaii (KPH) electronic medical record system (Aim 1). These databases will also be used to determine the incidence of HZO and how it has changed since the implementation of the HZ vaccine (Aim 2). To provide more detailed analysis of patient outcomes, medical record review will be performed with KPH records to determine how the vaccine impacts the severity and chronicity of HZO (Aim 3). To then compare the ocular morbidity associated with HZO to other ophthalmic conditions, we will be analyzing the Intelligent Research in Sight (IRIS) Registry through American Academy of Ophthalmology (Aim 4). By using multiple data sources, we aim to obtain generalizable results from large and diverse populations to characterize how HZ vaccination affects the incidence and clinical course of HZO. Our proposed study will provide clinically relevant information from a variety of populations on the morbidity caused by HZO, as well as the impact of the HZ vaccine on the development and course of HZO. These results could have significant public health implications and be used to formulate recommendations on the use of the vaccine from an ophthalmic perspective.